Tyrosine 537 within the Na+,K+-ATPase α-subunit is essential for AP-2 binding and clathrin-dependent endocytosis

Stefania Cotta Doné, Ingo B. Leibiger, Riad Efendiev, Adrian I. Katz, Barbara Leibiger, Per Olof Berggren, Carlos H. Pedemonte, Alejandro M. Bertorello

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57 Scopus citations

Abstract

In renal epithelial cells endocytosis of Na+,K+-ATPase molecules is initiated by phosphorylation of its α1-sub-unit, leading to activation of phosphoinositide 3-kinase and adaptor protein-2 (AP-2)/clathrin recruitment. The present study was performed to establish the identity of the AP-2 recognition domain(s) within the Na+,K+-ATPase α1-subunit. We identified a conserved sequence (Y537LEL) within the α1-subunit that represents an AP-2 binding site. Binding of AP-2 to the Na+,K+-ATPase α1-subunit in response to dopamine (DA) was increased in OK cells stably expressing the wild type rodent α-sub-unit (OK-WT), but not in cells expressing the Y537A mutant (OK-Y537A). DA treatment was associated with increased α1-subunit abundance in clathrin vesicles from OK-WT but not from OK-Y537A cells. In addition, this mutation also impaired the ability of DA to inhibit Na+,K+-ATPase activity. Because phorbol esters increase Na+,K+-ATPase activity in OK cells, and this effect was not affected by the Y537A mutation, the present results suggest that the identified motif is specifically required for DA-induced AP-2 binding and Na+,K+-ATPase endocytosis.

Original languageEnglish (US)
Pages (from-to)17108-17111
Number of pages4
JournalJournal of Biological Chemistry
Volume277
Issue number19
DOIs
StatePublished - May 10 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Doné, S. C., Leibiger, I. B., Efendiev, R., Katz, A. I., Leibiger, B., Berggren, P. O., Pedemonte, C. H., & Bertorello, A. M. (2002). Tyrosine 537 within the Na+,K+-ATPase α-subunit is essential for AP-2 binding and clathrin-dependent endocytosis. Journal of Biological Chemistry, 277(19), 17108-17111. https://doi.org/10.1074/jbc.M201326200